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Are age-related changes in cortical motor representations linked with facilitation/inhibition in the primary motor cortex?

Melina Hehl1*, Stephan P. Swinnen1, 2 and Koen Cuypers1, 3
  • 1 Movement Control and Neuroplasticity Research Group, Department of Kinesiology, Biomedical Sciences Group, KU Leuven, Belgium
  • 2 Leuven Research Institute for Neuroscience & Disease (LIND), Belgium
  • 3 REVAL Rehabilitation Research Center, Belgium

Introduction With healthy aging, the brain undergoes physiological and anatomical changes such as reorganization and remodeling (Cabeza, 2002; Dinse, 2006), which are at least partly responsible for the age-related decline in sensorimotor control and function (Bhandari et al., 2016). Specifically, older adults often show a higher variability in their movements, slower reaction times (Bedard et al., 2002; Wu and Hallett, 2005; Seidler et al., 2010; Hermans et al., 2018; Hermans et al., 2019), impaired coordination skills (Greene and Williams, 1996; Swinnen et al., 1998; Serrien et al., 2000; Heuninckx et al., 2004), and a generally lower performance level (Voelcker-Rehage, 2008). In this study, transcranial magnetic stimulation (TMS) was used to identify the link between age-related changes in cortical motor representation and metrics of glutamatergic and gamma-aminobutyric acid (GABA) functionality in the primary motor cortex (M1). Although there has been a growing body of evidence for age-related changes in TMS parameters in M1, few studies (Heise et al., 2013) addressed the changes of those parameters over the full adult lifespan to determine when those changes occur. Furthermore, it has remained unclear if/how the motor representation changes over the lifespan. To date, a more diffuse expansion of the motor map in older adults of the first dorsal interosseus (FDI) has been reported (Bernard and Seidler, 2012) and a difference in the age-related changes of hand muscle representations has been indicated by a TMS mapping study by Coppi et al. (2014) that reported an age-related decrease of the non-dominant abductor pollicis brevis (APB) representation, while the representation of the abductor digiti minimi (ADM) did not change significantly. However, although older individuals struggle more with handling smaller objects (picking up a coin) as compared to bigger items (grasping a glass), it is not clear yet if these age-related motor differences can be linked to changes in TMS parameters. Therefore, the first aim of the present study was to investigate how the motor representation of the FDI and ADM muscle, representative for pinch grasp and full-grasp tasks respectively, changed over the lifespan. The second aim was to identify if the motor representation is linked with glutamatergic and/or gamma-aminobutyric acid (GABA) functionality assessed with respectively intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) through a paired-pulse (PP) TMS protocol. Methods Eighteen healthy volunteers from the full lifespan (age range 18-69 years, average 39.61 ± 16.92 SD, 11 female, 2 left-handed, see Table 1) were to date included in this cross-sectional study. Recruitment was done in Flanders, Belgium at university and community level. Participants gave written informed consent prior to study participation according to the Declaration of Helsinki. The study was approved by the local ethics committee (University Hospital Leuven; reference S62231). Prior to inclusion subjects were screened for TMS contraindications (Wassermann, 1998), neurological medical history, medication and cognitive function. Grasp force and pinch force were measured bilaterally using respectively a hydraulic hand dynamometer (Model SH5001, Saehan Corporation, Masan, Korea) and a pinch force sensor (LCM302-200N, Omega Engineering Inc., Norwalk, USA). Electromyography (EMG) signals for the FDI and ADM muscle contralateral to the investigated hemisphere were collected using surface Ag-electrodes (Bagnoli™ DE-2.1 EMG Sensors, Natick, MA, United State), mounted to the muscle belly. A reference electrode was placed on the dorsal ipsilateral wrist. Raw EMG signals were amplified (gain = 1000), filtered (band pass filter 20-2000 Hz), digitized at 5000 Hz (CED 1401 micro, CED Limited, Cambridge, UK), and stored on PC for offline analysis. Cortical motor representation maps and TMS-derived glutamatergic and GABA-ergic metrics were collected for the left and right FDI and the ADM using a Magventure X100 stimulator (MagVenture A/S, Farum, Denmark). A 70mm figure-of-eight shaped coil (MC-B70) was used for single- (SP) or PP stimulation. A virtual 1cm-spaced grid was projected on the subject’s head using neuronavigation (Brainsight, Rogue Research Inc, Montreal, Quebec, Canada). For each hemisphere a standardized procedure was carried out: [1] the hotspot which was defined as the scalp location resulting in the highest motor evoked potential (MEP) after five consecutive stimuli of the relaxed FDI muscle, [2] the resting motor threshold (rMT) was defined as the lowest stimulation intensity evoking MEPs with an amplitude larger than 50 µV peak-to-peak in at least five of ten consecutive trials at rest, [3] the motor representation was mapped (see Figure 1) whereby TMS intensity was set at 115% rMT and 8 consecutive pulses were applied per location with an interstimulus interval (ISI) of 3s ± 20% and other mapping parameters were identical to Meesen et al. (2011) and Cuypers et al. (2013), [4] glutamatergic and GABAA-ergic metrics were assessed using respectively ICF and SICI. The conditioning stimulus (CS) was set at 80% rMT and the test stimulus (TS) was adjusted to elicit unconditioned MEP amplitudes (~1mV peak-to-peak). For SICI, ISI was set at 3ms and for ICF at 10ms. The SICI/ICF measurement consisted of 45 trials over M1 (15 SP, 15 PP - 3ms ISI and 15 PP - 10ms ISI in semi-randomized order). SICI and ICF were expressed as a ratio (mean PP amplitude/mean SP amplitude). All TMS measurements were administered bilaterally in a semi-randomized order (left or right hemisphere). Results Based on preliminary data of this ongoing study, we showed first that although there was a significant decrease in grip force for the dominant and non-dominant hand (GRIP DOM: Spearman’s rho = -0.469, p = 0.049; GRIP NON-DOM: Spearman’s rho = -0.484, p = 0.042) and a significant decrease in pinch force for the non-dominant but not for the dominant hand (PINCH DOM: Spearman’s rho = -0.452, p = 0.059; PINCH NON-DOM: Spearman’s rho = -0.527, p = 0.025, see Figure 2) with advancing age, Spearman’s correlations revealed no significant changes between map area and age for the different combinations of muscle (FDI, ADM) and hemisphere (dominant, non-dominant) (all, p > 0.05). Second, a significant positive relationship between AREA and ICF of the dominant FDI was found (Spearman’s rho = 0.564, p = 0.018, see Figure 3B), indicating that increased cortical representation is related to increased glutamatergic facilitation. All other links between motor representations and measures of SICI/ICF were reported as non-significant (all, p > 0.05, see Figure 3 & 4). Finally, trends between age and measures of SICI/ICF were reported, suggesting that higher age may be linked with decreased inhibition and increased facilitation (see Figure 5 & 6 and Table 2). Conclusion Based on our preliminary findings, we can conclude that: [1] age-related changes in grip and pinch force are not related to changes in cortical representation, [2] cortical representation for the dominant FDI is positively linked with glutamatergic facilitation, and [3] statistical trends suggest that higher age may be linked with decreased inhibition and increased facilitation.

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Keywords: Aging, transcrancial magnetic stimulation (TMS), Short-interval cortical inhibition, Intracortical facilitation (ICF), Cortical representation

Conference: 13th National Congress of the Belgian Society for Neuroscience , Brussels, Belgium, 24 May - 24 May, 2019.

Presentation Type: Poster presentation

Topic: Behavioral/Systems Neuroscience

Citation: Hehl M, Swinnen SP and Cuypers K (2019). Are age-related changes in cortical motor representations linked with facilitation/inhibition in the primary motor cortex?. Front. Neurosci. Conference Abstract: 13th National Congress of the Belgian Society for Neuroscience . doi: 10.3389/conf.fnins.2019.96.00054

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Received: 24 Apr 2019; Published Online: 27 Sep 2019.

* Correspondence: Ms. Melina Hehl, Movement Control and Neuroplasticity Research Group, Department of Kinesiology, Biomedical Sciences Group, KU Leuven, Leuven, 3000, Belgium, melina.hehl@student.kuleuven.be